Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease.

BACKGROUND: Vitamin D metabolites support innate immune responses to Mycobacterium tuberculosis. Data from phase 3, randomized, controlled trials of vitamin D supplementation to prevent tuberculosis infection are lacking. METHODS: We randomly assigned children who had negative results for M. tuberculosis infection according to the QuantiFERON-TB Gold In-Tube assay (QFT) to receive a weekly oral dose of either 14,000 IU of vitamin D3 or placebo for 3 years. The primary outcome was a positive QFT result at the 3-year follow-up, expressed as a proportion of children. Secondary outcomes included the serum 25-hydroxyvitamin D (25[OH]D) level at the end of the trial and the incidence of tuberculosis disease, acute respiratory infection, and adverse events. RESULTS: A total of 8851 children underwent randomization: 4418 were assigned to the vitamin D group, and 4433 to the placebo group; 95.6% of children had a baseline serum 25(OH)D level of less than 20 ng per milliliter. Among children with a valid QFT result at the end of the trial, the percentage with a positive result was 3.6% (147 of 4074 children) in the vitamin D group and 3.3% (134 of 4043) in the placebo group (adjusted risk ratio, 1.10; 95% confidence interval [CI], 0.87 to 1.38; P = 0.42). The mean 25(OH)D level at the end of the trial was 31.0 ng per milliliter in the vitamin D group and 10.7 ng per milliliter in the placebo group (mean between-group difference, 20.3 ng per milliliter; 95% CI, 19.9 to 20.6). Tuberculosis disease was diagnosed in 21 children in the vitamin D group and in 25 children in the placebo group (adjusted risk ratio, 0.87; 95% CI, 0.49 to 1.55). A total of 29 children in the vitamin D group and 34 in the placebo group were hospitalized for treatment of acute respiratory infection (adjusted risk ratio, 0.86; 95% CI, 0.52 to 1.40). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS: Vitamin D supplementation did not result in a lower risk of tuberculosis infection, tuberculosis disease, or acute respiratory infection than placebo among vitamin D-deficient schoolchildren in Mongolia. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02276755.).

Changes in Vascular Function from Preconception to Postpartum Among Mongolian Women.

Background: Pregnancy is associated with physiological changes to meet the metabolic demands of the growing fetus. To understand adverse pregnancy outcomes it is important to establish vascular changes throughout pregnancy. We examined longitudinal changes in vascular measurements from prepregnancy through postpartum. Materials and Methods: Seventy women planning to conceive in Ulaanbaatar, Mongolia enrolled in this prospective study. Within 6 months, 44 (63%) had conceived; of which 36 (82%) delivered. Ten (28%) developed complex pregnancies and were analyzed separately. Vascular measures included central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), augmentation index corrected for heart rate of 75 beats/minute (AIx-75), and pulse wave velocity (PWV). Measurements were performed at prepregnancy, second trimester (22-24 weeks), third trimester (34-36 weeks), and 2 months postpartum. Missing values (n = 0-6 per time period) were replaced by multiple imputation. A repeated measures analysis of variance analyzed changes within individual women over the four time points adjusted for age, parity, and body mass index. Results: We observed significant reductions from prepregnancy to second trimester for mean Alx-75 (17.1%-12.6%; p = 0.006) and cSBP (91.7-86.8 mmHg; p = 0.03) but not for cDBP or PWV. Both mean AIx-75 and cSBP increased in third trimester. In the postpartum, cSBP returned to prepregnancy levels, whereas AIx-75 exceeded prepregnancy levels, although this fell short of significance (p = 0.09). Similar vascular patterns were observed in women with complex pregnancies for AIx-75; however, PWV increased from the second trimester and remained higher through postpartum, although not significant. Conclusion: In Mongolian women, we observed a decrease in AIx-75 and cSBP from prepregnancy through second trimester, which resolved postpartum. These results provide an understanding of changes across pregnancies in an Asian country. Future studies should assess vascular changes across pregnancies to determine if it can predict conditions such as pre-eclampsia.

Maternal Pregnancy Hormone Concentrations in Countries with Very Low and High Breast Cancer Risk.

BACKGROUND: Breast cancer rates in Asia are much lower than in Europe and North America. Within Asia, rates are lower in Mongolia than in neighboring countries. Variation in pregnancy exposure to endogenous hormone concentrations may explain the differences, but data are lacking. METHODS: We measured maternal serum progesterone, prolactin, estradiol and estrone concentrations in the second half of pregnancy in a cross-sectional study of urban (n = 143-194 depending on the analyte) and rural (n = 150-193) Mongolian women, and U.S. women from Boston (n = 66-204). Medical records provided information on maternal and perinatal factors. Geometric mean hormones were estimated from standard linear models with the log-hormone as the dependent variable and country as the independent variable adjusted for maternal and gestational age at blood draw. RESULTS: Mean concentrations of prolactin (5722 vs. 4648 uIU/mL; p < 0.0001) and estradiol (17.7 vs. 13.6 ng/mL; p < 0.0001) were greater in Mongolian than U.S. women, while progesterone (147 vs. 201 ng/mL; p < 0.0001) was lower. Mean hormone concentrations were similar in rural and urban Mongolian women. Results were generally similar, with additional adjustment for gravidity, parity, height, body mass index at blood draw, education and alcohol use during pregnancy, and when stratified by offspring sex or parity. CONCLUSIONS: Mongolian women had greater concentrations of prolactin and estrogen and lower concentrations of progesterone than U.S. women, while hormone concentrations were similar in rural and urban Mongolian pregnancies. IMPACT: These data do not support the hypothesis that estrogen concentrations in pregnant women are lower in Mongolian compared with Caucasian women.